[Concentration of antibiotics in various jaw tissues: concentration of erythromycin (2)].
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Biomedical subjects
Publications and source records attributed to F Santoro.
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The appearance of autoantibodies was investigated during the course of Schistosoma mansoni infection in C57Bl/6 mice. Anti-liver autoantibodies or lymphocyte-reactive alloantibodies were detected respectively without cell-mediated immunity against liver antigen or lymphocytotoxic activity. Anti-liver, anti-DNA, anti-Ig and anti-lymphocyte antibodies were shown 6-7 weeks after the beginning of the infection concomitantly with the increase of immunoglobulin levels and circulating immune complexes. At this period, the antibody response to polyvinylpyrrolidone (PVP) was increased and the injection of spleen cells from day-45-infected mice to uninfected recipients increased the anti-PVP antibody response. Conversely, the injection of spleen cells from uninfected to infected mice did not modify the anti-PVP Ab response. After 6 weeks of infection, the basal thymidine incorporation of spleen cells was increased contrasting with the marked inhibition of spleen cell response to PHA. The present data are consistent with the induction of a polyclonal non-specific B cell activation by S. mansoni.
It was previously reported that Schistosoma mansoni schistosomula in the presence of IgG activate complement through the classical pathway (CCP). In the present work we have demonstrated that schistosomula incubated with IgG peptides resulting from IgG hydrolysis by schistosomula proteases are able to initiate complement activation through CCP, since a marked consumption of C1, C4, and C2 was observed. Our results eliminate an eventual direct action of the substances released by schistosomula on the activation of CCP. The first step of CCP activation required the preliminary binding of IgG peptides on the schistosomula surface. This interaction induced an increase in the C1q uptake by schistosomula. Since the involvement of the Fc portion of IgG molecules has been clearly evidenced, in this case the peripheral globular subunits of C1q recognize the CH2 region on IgG peptides or intact IgG molecules. By this mechanism, the local consumption of complement around schistosomula could contribute to its survival in the host.
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Complement-dependent cytotoxic antibodies were found in 54% of Schistosoma mansoni infected patients from Burundi and in 69 to 78% of Schistosoma mansoni ninfected Brazilian patients. The levels of cytotoxic Ab were not statistically different in sera from infected mothers and from their newborn children, suggesting a transfer through the placenta. A sandwich radioimmunoassay (SRIA) and the Radioimmunoprecipitaion-PEG assay (RIPEGA) technique were used in order to detect respectively total schistosome circulating soluble antigens (CSA) and schistosome antigen '4' in sera from infected patients. An inverse relationship was found between the presence of cytotoxic Ab and both total CSA and antigen '4'. The cytotoxic Ab and total CSA levels were followed in five Erythrocebus patas monkeys for 30 weeks after Schistosoma mansoni infection. As in human schistosomiasis the presence of cytotoxic Ab was found to be inversely correlated with the presence of total CAS. The blocking role of Schistosoma mansoni antigens in a complexed form was suggested by the inhibitory effect of the ultracentrifugation pellet of infected human serum on the cytotoxic activity. Moreover, the CSA absorption of infected monkey serum by passage through an anti-CSA immunosorbent significantly increased the cytotoxic activity. Possible mechanisms for the inhibitory role of circulating immune complexes on complement-dependent cytotoxic activity are discussed.
C1q-binding immune complexes (C1C), anti-IgG antibodies (anti-IgG Ab), and complement levels were investigated in the serum of 37 patients with ankylosing spondylitis (AS). In all these studies the mean levels observed in patients with AS were similar to those in 31 normal subjects. Moreover, no significative difference in either CIC or anti-IgG Ab levels was observed when the patients were classified in different clinical forms according to the localisation (peripheral and central) or to the gravity (mild and severe) of the AS. In a parallel study increased CIC and anti-IgG Ab levels were found in most of the 81 patients with seropositive or seronegative rheumatoid arthritis.
Circulating immune complexes (CIC), anti-IgG, anti-DNA, and anti-collagen autoantibodies (Ab) were investigated in sera from patients with South American leishmaniasis. No significant levels of anti-DNA or anti-collagen autoantibodies were observed. Only a few patients with cutaneous leishmaniasis or with only one mucocutaneous lesion showed values for CIC and anti-IgG Ab higher than those in the control group. In contrast, both CIC and anti-IgG Ab were demonstrated in most patients with several lesions due to mucocutaneous leishmaniasis (MMC). Moreover, a close correlation was noticed between the detection of CIC and anti-IgG Ab in MMC patients. This relationship suggested that part of the detected CIC could have been formed by IgG-anti-IgG complexes. The involvement of these immunopathologically active substances in the clinical evolution of mucocutaneous leishmaniasis is discussed.
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In earlier studies we have found that activation of the classical complement pathway (CCP) by the immature schistosomes involves the presence of IgG. By investigating the first step of this activation we have demonstrated in the present work that binding of C1q to schistosomula can occur by two different routes: 1) directly, by specific C1q receptors, and 2) indirectly through the IgG previously attached to Fc receptors present on the parasite surface. Only this second mechanism appears to be involved in CCP activation by schistosomula. Moreover, certain low m.w. schistosome antigens (less than 20,000), which activate CCP, also directly fixed C1q. In this case, IgG are not required for C activation. The presence of receptors for host protein, essentially in 2- to 3-hr-old schistosomula, i.e., the life stage of Schistosoma mansoni that are first in contact with the host, could be the first mechanism by which the schistosomes evade the immune attack.
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Circulating schistosome antigens (CSA), circulating immune complexes (CIC) and C3 breakdown product - C3d - were investigated in human schistosomiasis in comparison to the S. mansoni egg count. A close relationship was observed between the mean number of eggs/g of stool and the detection of CSA (evaluated by the radioimmunoprecipitation-PEG assay - Ripega), CIC (Clq-binding test) and C3d levels (quantitated by radial immunodiffusion). All the patients with more than 500 S. mansoni eggs/g of stool also presented antigen '4', specific of the genus Schistosoma, in the serum. A significant correlation was noticed between levels of CSA and CIC. This suggests the involvement of several schistosome antigens in the detected CIC. No relationship was noted between CIC and C3d levels. In contrast, there was a highly significant correlation between levels of CSA and C3d. The interaction between certain schistosome antigens and the complement system is discussed.